Mutations of the Gene in Non-Small Cell Lung Cancer: Association with Aberrant Localization of Cx43 Protein Expression and Tumor Progression.

: The Connexin43 () gene is a suspected tumor suppressor gene, as re-expressed wild-type genes reduce the malignancy potential of tumor cells. However, the role of gene expression in human lung tumorigenesis remains unclear. Tumor tissues from 165 primary lung cancer patients were collected to study Cx43 protein expression and gene mutations using immunohistochemistry and direct DNA sequencing. In addition, genes with or without mutations were transfected to CL-3 human lung cancer cells to confirm the function of these mutant forms of the gene. Aberrant localization of Cx43 protein in the nucleus and cytoplasm of tumor cells was detected in 14 out of 165 non-small cell lung cancer (NSCLC) patients. Mutations in the gene were also found in patients with aberrant Cx43 localization, and transfection of these mutant genes into lung cancer cells enhanced their proliferation. To our knowledge, this is the first study to demonstrate gene mutations in human lung neoplasm, supporting the hypothesis that Cx43 may function as a tumor suppressor in some lung cancer patients. Additionally, the findings suggest an association between aberrant localization of Cx43 protein expression and tumor progression.